Sibling History Research Articles

Parental transmission of type 2 diabetes mellitus among patients attending a tertiary care hospital

Problem consideredType 2 Diabetes Mellitus is a heritable condition. Some studies suggest a strong maternal association while others claim paternal transmission of diabetes to be more significant. The present study was aimed at identifying the role of parental transmission in Type 2 diabetic patients with family history of diabetes. MethodsThis was a cross-sectional study carried out among individuals diagnosed with Type 2 Diabetes Mellitus (DM) and having a family history of the same attending the General Medicine OPD in a tertiary care hospital. Consenting consecutive patients fulfilling the inclusion criteria were enrolled into the study. Demographic characteristics, age at onset of Type 2 Diabetes and parental history of the disease were obtained in detail. ResultsOf the 174 participants enrolled into the study nearly 66% were males. Maternal history of DM (65%) was more commonly observed as compared to paternal history (57%) and nearly 23% had a history of both parents being diabetic. Fifty two percent gave a sibling history of type 2 DM. Siblings of patients with affected mothers had a greater likelihood of diabetes (77.8%) than those with affected fathers (51%) (P = 0.001). More males had a brother who was diabetic (66%), likewise more females had a sister who was diabetic (55%). ConclusionMaternal inheritance of DM appears to be more common and there is a significant association of type 2 diabetes among siblings of patients with affected mothers. This apparent association is an area that needs to be explored further.

Tobacco smoking, family history, and the risk of nasopharyngeal carcinoma: a case-referent study in Hong Kong Chinese.

This study aimed to investigate the associations of tobacco smoking and family history of nasopharyngeal carcinoma (NPC) with the risk of NPC in Hong Kong Chinese. Between June 2010 and December 2012, we conducted a case-referent study with 352 incident cases and 410 referents in Hong Kong. We collected information on tobacco smoking and family history of NPC via face-to-face interviews. There were 174 (49.4%) and 131 (32.0%) ever-smokers among cases and referents, respectively. The adjusted odds ratio (OR) for NPC related to current smoking was 1.67 [95% confidence interval (CI) 1.06, 2.61]. Exposure-response relationships were observed between years and total pack-years of smoking, and NPC risk (p = 0.001 and p = 0.018, respectively). History of NPC in first-degree relatives was associated with an increased NPC risk (adjusted OR = 4.52, 95% CI 2.39, 8.55). The increased NPC risk associated with sibling history (adjusted OR = 6.80, 95% CI 2.63, 17.56) was higher than that for parental history (adjusted OR = 3.04, 95% CI 1.27, 7.25). The adjusted OR for ever-smokers with family history using never-smokers without family history as the reference was 4.54 (95% CI 1.67, 12.34). This study verified the important roles of tobacco smoking and family history on NPC risk among Hong Kong Chinese. The provided evidence supported the knowledge that both environmental exposures and inherited susceptibility contributed to the risk of NPC.

Treatment Approach of a Patient Affected by Both Argininosuccinic Aciduria and Methylmalonic Aciduria

Most of the inborn errors of metabolism (IEM) are autosomal recessively inherited and they are more frequent in the countries where consanguineous marriages are commonly practiced. Rarely, more than one IEM are seen in the siblings of one family or in the same sibling. Here we report a patient with both argininosuccinic aciduria (ASA) and methylmalonic acidemia (MMA) and our therapeutic approach. First sibling of the family died with MMA, second sibling was diagnosed with ASA, and third sibling was diagnosed with both ASA and MMA. Here we report terapeutic approach of this patient. Dietary regimen of the patient was planned with MMA being the basis. When a patient was admitted with a history of sibling with an IEM, possibility of another disorder should always be kept in mind particularly in the countries that consanguineous marriages are commonly practiced.

The Prevalence and Sociodemographic Risk Factors of Enuresis Nocturna among Elementary School-age Children.

Introduction and Aim:Many etiological reasons are blamed for enuresis nocturna (EN). The aim of this study was to research prevalence and severity of EN among elementary school-age children and sociodemographic risk factors related to it.Materials and Methods:The study was performed in three elementary schools in Ankara, Turkey between January and May 2011. It was planned to have 2500 students of 6–14 ages in the study. The questionnaire, which consisted of questions, aiming to evaluate the EN condition of participants and their characteristics, were distributed to the parents. It was observed that 2314 participants’ questionnaires (92.56%) were in accordance with evaluation criteria.Statistical Analysis:The relation between EN and the sociodemographic factors was evaluated through Chi-square test and logistic regression analysis.Results:The mean age of 2314 participants was 9.21 ± 2.08. 48.5% (n = 1123) of the students were male and 51.5% (n = 1191) were female. While the general EN prevalence was 9.9% (n = 230); 10.7% (n = 120) for males, as 9.2% (n = 110) for females. Statistical significant difference was determined between the two groups, with EN and without EN, regarding age groups (P < 0.001), education level of parents (P < 0.001, P < 0.001), and the number of sibling (P = 0.002), income level (P < 0.001), and positive family history (P < 0.001). However, logistic regression analysis revealed that there was a significant difference only between EN and age groups (odds ratio [OR] =4.42, P < 0.001), education level of mother (OR = 2.13, P = 0.017) and family history (OR = 0.12, P < 0.001).Conclusions:As a consequence, such factors as age groups, education level of parents, positive family history could be accepted as a risk of concerning EN. It is important to perform a detailed evaluation on population, carrying risk of having EN.

Mutations in EDA and EDAR Genes in a Large Mexican Hispanic Cohort with Hypohidrotic Ectodermal Dysplasia.

Mutations in EDA and EDAR Genes in a Large Mexican Hispanic Cohort with Hypohidrotic Ectodermal Dysplasia.

Maternal immunization with pneumococcal 9-valent conjugate vaccine and early infant otitis media

A randomized trial of an investigational 9-valent pneumococcal conjugate vaccine (PCV-9) or placebo given to pregnant women during the last trimester to prevent early infant otitis media (OM) was conducted. All infants received Prevnar® at 2, 4, 6, and 12 months. Clinic and adverse event records were reviewed to identify OM. Variables significantly related to acute OM by age 6 months (p<0.05) were: vaccine group (9 valent or placebo), sibling history of tympanostomy tubes, upper respiratory infection, and number of clinic visits by 6 months. Infant OM rates were similar between 6 and 12 months (58% and 56%). Results suggested that immunizing pregnant women with PCV-9 increased infants’ risk of acute OM in the first 6 months of life, and this correlated with decreased infant antibody responses to their infant Streptococcus pneumoniae vaccine serotypes, but did not influence antibody responses to 3 other serotypes two of which were in maternal vaccine (types 1 and 5) and one was a control (type 7F). Explanations for these results include dampening of infant antibody production by high levels of passively acquired maternal pneumococcal antibodies and/or altered B lymphocyte immune responses in infants exposed to these specific polysaccharide antigens in utero.

PO-0610 Neonatal Readmission For Indirect Hyperbilirubinemia In Al Ahsa, Saudi Arabia

Background Causes and severity of neonatal indirect hyperbilirubinemia (IH) vary geographically. Understanding local differences may assist in prevention of complications. Objective To study the causes and severity of IH in readmitted neonates in Al Ahsa district. Methods Records of all neonates readmitted for IH to Almana General Hospital at Al Ahsa between 2009 and 2013 were reviewed. Data included: maternal and neonatal characteristics, laboratory results, associated causes of IH and interventions. Results 323 neonates were readmitted for IH (gestational age: 38 ± 1.8 weeks, birth weight: 3023 ± 513 g and males: 66%). The age and weight at readmission were 125 ± 770 h and 2923 ± 508 g respectively. History of previous jaundiced sibling was documented in 15%. The most common cause for IH was G6 PD deficiency (39.9%), followed by ABO incompatibility (12%) and breast milk jaundice (11%). The cause could not be determined in 31%. Based on 2004-AAP phototherapy guideline, 30% infants were categorised as at lower risk, 58% at medium and 14% at higher risk. The highest serum bilirubin during readmission was 322 ± 59 µmol/L (range:198–686 µmol/L). All infants received phototherapy, and 2 required blood exchange transfusions. One case of kernicterus was documented (highest serum bilirubin: 686 µmol/L) with no mortality. The median length of hospital stay was 2 days. 25(7.7%) required more than one admission. Conclusions In Al Ahsa, the commonest cause of neonatal indirect hyperbilirubinemia is G6 PD deficiency. Screening for G6 PD deficiency and close postnatal follow up are recommended.

Glaucoma knowledge in a black community in Toronto

Background: Black people are at high risk of glaucoma. Routine eye exams are the only way of identifying early glaucoma for treatment and blindness prevention. Public education on glaucoma risk factors and detection may be an important public health strategy to encourage those at high risk to have their eyes checked. Purpose: To evaluate glaucoma knowledge (including presentation, risk factors and detection) and associated socio-demographic factors in a black community in Toronto to aid the development of future public education programs. Materials and Methods: Questionnaire surveys from 5 black people centered churches or organizations. Results: The mean age of participants (n=201) was 48.7 years. Most participants reported glaucoma can cause blindness (88.6%) and run in families (76.0%). However, only few participants (4%) correctly reported glaucoma affects peripheral vision. Over 1 in 4 participants (26.7%) reported incorrectly glaucoma always causes eye symptoms. Less than half of the participants knew black people are at higher risk of glaucoma (48.7%) and glaucoma most likely affects people 40 years or older (46.2%). A history of parents or siblings with glaucoma was not associated with better knowledge of three established glaucoma risk factors (40 years or over, African origin and positive family history). Participants 40 years or older did not have greater knowledge than those under 40 that older people are at higher risk of developing glaucoma (prevalence ratio (PR)=0.90, 95% confidence interval (CI) 0.63-1.26). Participants with and without postsecondary education equally reported that eye examinations are the only way to identify glaucoma (PR=1.02, 95% CI 0.72-1.46). Poverty was associated with lower levels of knowledge of the aforementioned three glaucoma risk factors and that glaucoma is identified through eye examinations. Conclusion: Glaucoma knowledge in Toronto's black community is inadequate. Education about glaucoma presentation, risk factors and detection should be prioritized in this high-risk group.

Update of the German Diabetes Risk Score and external validation in the German MONICA/KORA study

AimsSeveral published diabetes prediction models include information about family history of diabetes. The aim of this study was to extend the previously developed German Diabetes Risk Score (GDRS) with family history of diabetes and to validate the updated GDRS in the Multinational MONItoring of trends and determinants in CArdiovascular Diseases (MONICA)/German Cooperative Health Research in the Region of Augsburg (KORA) study. MethodsWe used data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study for extending the GDRS, including 21,846 participants. Within 5 years of follow-up 492 participants developed diabetes. The definition of family history included information about the father, the mother and/or sibling/s. Model extension was evaluated by discrimination and reclassification. We updated the calculation of the score and absolute risks. External validation was performed in the MONICA/KORA study comprising 11,940 participants with 315 incident cases after 5 years of follow-up. ResultsThe basic ROC-AUC of 0.856 (95%-CI: 0.842–0.870) was improved by 0.007 (0.003–0.011) when parent and sibling history was included in the GDRS. The net reclassification improvement was 0.110 (0.072–0.149), respectively. For the updated score we demonstrated good calibration across all tenths of risk. In MONICA/KORA, the ROC-AUC was 0.837 (0.819–0.855); regarding calibration we saw slight overestimation of absolute risks. ConclusionsInclusion of the number of diabetes-affected parents and sibling history improved the prediction of type 2 diabetes. Therefore, we updated the GDRS algorithm accordingly. Validation in another German cohort study showed good discrimination and acceptable calibration for the vast majority of individuals.

Family history of venous thromboembolism (VTE) and risk of recurrent hospitalization for VTE: a nationwide family study in Sweden

Data concerning the importance of a family history of venous thromboembolism (VTE) for the risk of recurrent VTE are sparse. The aim of this nationwide study was to determine whether a family history of VTE is a risk factor for recurrent hospitalization for unprovoked VTE (deep vein thrombosis of the lower extremities or pulmonary embolism). We linked Multigeneration Register data on individuals aged 0-77years to the Swedish nationwide Hospital Discharge Register data for the period 1987-2009 to compare the risk of hospitalization for unprovoked recurrent VTE among individuals with and without a parental or sibling history of VTE. We calculated hazard ratios (HRs) to determine the familial HR for recurrent hospitalization for VTE. The risk of recurrent VTE hospitalization was 1.20 (95% confidence interval [CI]1.10-1.32) for individuals with affected parents, and 1.30 (95%CI1.14-1.49) for those with affected siblings. The risk of recurrent VTE hospitalization in individuals with two affected parents was 1.92 (95%CI1.44-2.58). There was an interaction between age at diagnosis of VTE and a family history of VTE, with a family history having a stronger effect on VTE risk in younger patients. We conclude that a family history of VTE is a modest risk factor for recurrent VTE hospitalization in Sweden.

The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin

Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. One thousand nine hundred and fifty-five subjects aged 16-77years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P=0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.

Role of maternal elimination diets and human milk IgA in the development of cow's milk allergy in the infants

The role of maternal avoidance diets in the prevention of food allergies is currently under debate. Little is known regarding the effects of such diets on human milk (HM) composition or induction of infant humoral responses. To assess the association of maternal cow's milk (CM) avoidance during breastfeeding with specific IgA levels in HM and development of cow's milk allergy (CMA) in infants. We utilized HM and infant serum samples from a prospective birth cohort of 145 dyads. Maternal serum and HM samples were assessed for casein and beta-lactoglobulin (BLG)-specific IgA and IgG by ELISA; 21 mothers prophylactically initiated a strict maternal CM avoidance diet due to a sibling's history of food allergy and 16 due to atopic eczema or regurgitation/vomiting seen in their infants within the first 3 months of life. Infants' sera were assessed for casein and BLG-specific IgG, IgA and IgE; CMA was confirmed by an oral food challenge. The impact of HM on BLG uptake was assessed in transcytosis assays utilizing Caco-2 intestinal epithelial cell line. Mothers avoiding CM had lower casein- and BLG-specific IgA in HM than mothers with no CM restriction (P = 0.019 and P = 0.047). Their infants had lower serum casein- and BLG-specific IgG(1) (P = 0.025 and P < 0.001) and BLG-specific IgG(4) levels (P = 0.037), and their casein- and BLG-specific IgA levels were less often detectable than those with no CM elimination diet (P = 0.003 and P = 0.007). Lower CM-specific IgG4 and IgA levels in turn were associated with infant CMA. Transcytosis of BLG was impaired by HM with high, but not low levels of specific IgA. Maternal CM avoidance was associated with lower levels of mucosal-specific IgA levels and the development of CMA in infants. HM IgA may play a role in preventing excessive, uncontrolled food antigen uptake in the gut lumen and thereby in the prevention of CMA.

Family history of coronary heart disease and the incidence and progression of coronary artery calcification: Multi-Ethnic Study of Atherosclerosis (MESA)

ObjectiveWe evaluated family history as a predictor of incident and progressive coronary artery calcium (CAC) using data from the Multi-Ethnic Study of Atherosclerosis (MESA). BackgroundMESA is a multi-center prospective study of 6814 asymptomatic individuals. The relationship between family history of coronary heart disease (CHD) and CAC incidence or progression has not been described previously. MethodsA total of 5099 participants had detailed information about family history of CHD (late versus premature and parental versus sibling history). The mean time between CAC scans was 3.1 ± 1.3 years. The association of late versus premature family history was assessed against CAC change using multivariate regression model adjusted for demographics and cardiac risk factors. ResultsA family history of premature CHD was associated with an odds ratio (OR) of 1.55 (p < 0.01) for incident development of CAC after adjusting for risk factors and demographics. A premature family history was associated with 14.4 units (p < 0.01) greater volume scores compared to those with no family history in similarly adjusted models by median regression analysis. A combined parental and sibling family history was associated with the greatest incidence and progression in demographic-adjusted models. Caucasians demonstrated the most consistent predictive relationship between family history of premature CHD and incidence (p < 0.01) and progression (p < 0.05) of CAC, though no significant interaction with ethnicity was noted. ConclusionsFamily history of premature CHD is associated with enhanced development and progression of subclinical disease, independent of other risk factors, in a multiethnic, population-based study.

Parent-reported otorrhea in children with tympanostomy tubes: incidence and predictors.

PurposeAlthough common in children with tympanostomy tubes, the current incidence of tympanostomy tube otorrhea (TTO) is uncertain. TTO is generally a sign of otitis media, when middle ear fluid drains through the tube. Predictors for otitis media are therefore suggested to have predictive value for the occurrence of TTO.ObjectiveTo determine the incidence of TTO and its predictors.MethodsWe performed a cohort study, using a parental web-based questionnaire to retrospectively collect data on TTO episodes and its potential predictors from children younger than 10 years of age with tympanostomy tubes.ResultsOf the 1,184 children included in analyses (total duration of time since tube placement was 768 person years with a mean of 7.8 months per child), 616 children (52%) experienced one or more episodes of TTO. 137 children (12%) had TTO within the calendar month of tube placement. 597 (50%) children had one or more acute TTO episodes (duration <4 weeks) and 46 children (4%) one or more chronic TTO episodes (duration ≥4 weeks). 146 children (12%) experienced recurrent TTO episodes. Accounting for time since tube placement, 67% of children developed one or more TTO episodes in the year following tube placement. Young age, recurrent acute otitis media being the indication for tube placement, a recent history of recurrent upper respiratory tract infections and the presence of older siblings were independently associated with the future occurrence of TTO, and can therefore be seen as predictors for TTO.ConclusionsOur survey confirms that otorrhea is a common sequela in children with tympanostomy tubes, which occurrence can be predicted by age, medical history and presence of older siblings.

Improving the Measurement of Maternal Mortality: The Sisterhood Method Revisited

BackgroundOver the past several decades the efforts to improve maternal survival and the consequent demand for accurate estimates of maternal mortality have increased. However, measuring maternal mortality remains a difficult task especially in developing countries with weak information systems. Sibling histories included in household surveys (most notably the Demographic and Health Surveys (DHS)) have emerged as an important source of maternal mortality data. Data have been mainly collected from women and have not been widely collected from men due to concerns about data quality. We assess data quality of histories obtained from men and the potential to improve the efficiency of surveys measuring maternal mortality by collecting such data.Methods and FindingsWe used data from 10 Demographic and Health Surveys (DHS) that have included a full sibling history in both their women’s and men’s questionnaires. We estimated adult and maternal mortality indicators from histories obtained from men and women. We assessed the completeness and accuracy of these histories using several indicators of data quality. Our study finds that mortality estimates based on sibling histories obtained from men do not systematically or significantly differ from those obtained from women. Quality indicators were similar when comparing data from men and women. Pooling data obtained from men and women produced narrower confidence intervals.ConclusionFrom experience across nine developing countries, sibling history data obtained from men appear to be a reliable source of information on adult and maternal mortality. Given that there are no significant differences between mortality estimates based on data obtained from men and women, data can be pooled to increase efficiency. This finding improves the feasibility for countries to generate robust empirical estimates of adult and maternal mortality from surveys. Further we recommend that male sibling histories be collected from all sample households rather than from a subsample.

Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden

BackgroundAlthough the heritability of atrial fibrillation (AF) has been determined, the relevance of family history of AF for the likelihood of recurrent hospitalization for AF is unknown. The aim of this nationwide study was to determine whether family history of AF is a risk factor of recurrent hospitalization for lone AF (LAF), i.e., AF with unknown etiology. The familial risk for first time LAF hospitalization was also determined and compared to the risk of recurrent hospitalization for LAF.MethodsWe examined whether family history of AF is a risk factor for recurrent hospitalization for LAF in the whole Swedish population. We linked Multigeneration Register data on individuals aged 0–60 years to Hospital Discharge Register data for the period 1987–2009 to compare LAF recurrent hospitalization risk among individuals with and without parental or sibling history of AF. We calculated hazard ratios (HRs) to determine the familial HR of recurrent hospitalization for LAF. Odds ratios (OR) were calculated for familial risk of first time LAF hospitalization.ResultsThe risk of recurrent LAF hospitalization was 1.23 (95% CI 1.17-1.30) for individuals with affected parents compared to 1.30 (95% CI 1.22-1.38) for those with affected siblings. After 10 years of follow up 50% of those without and 60% of those with family history had recurrent hospitalization for LAF. The risk of recurrent LAF hospitalization in individuals with two affected parents was 1.65 (95% CI 1.44-1.90). There was an interaction between age and family history, with family history having a weaker effect on LAF hospitalization risk in older age groups. The OR for first time LAF hospitalization was 2.08 (95% CI 2.02-2.15) for offspring with affected parents and 3.23 (95% CI 3.08-3.39) for individuals with affected siblings.ConclusionsFamily history of AF is a novel risk factor for recurrent LAF hospitalization. The higher recurrence hospitalization risk in multiplex families and younger individuals suggests a genetic contribution. However, the familial risk for recurrent LAF hospitalization was much lower than the risk for first time LAF hospitalization, suggesting that familial and possibly genetic factors are more important for first time LAF hospitalization than recurrent LAF hospitalization.

Prevalence of Asthma Symptoms and Associated Factors in Schoolchildren from Brazilian Amazon Islands

Objectives. To determine the prevalence of asthma symptoms among schoolchildren living on two different Brazilian Amazon islands and to identify the risk factors related to this condition. Methods. A cross-sectional study of 400 schoolchildren (5–8 years old) using written questionnaires produced by the International Study of Asthma and Allergies in Childhood, a skin prick test (allergic sensitization), and a stool examination (for helminthic infection). Nonparametric tests were carried out, and the risk factors were identified by logistic regression. Results. The prevalence of active asthma symptoms was markedly higher in children living on Outeiro Island (OI) than those living on Combú Island (CBI) (30.5% and 16.5%, respectively). The logistic regression identified several risk factors of asthma symptoms on CBI: parental history of asthma, night coughing in the past year, and “currently have a cat”. On OI, the major risk factors were parental history of asthma, personal history of eczema, having two or more older siblings, and night coughing in the past year. The risk factors in common on both the islands were night coughing in the past year and parental history of asthma. Conclusions. The prevalence of asthma symptoms was higher in those with a lifestyle closer to that observed in urban areas (i.e., better sanitation and hygiene), reinforcing the protective effect of a rural environment. Different risk factors were associated with asthma symptoms in schoolchildren living on OI and on CBI. This fact may reflect the environmental individuality and particularities of each island.

Genetic and Familial Environmental Influences on the Risk for Drug Abuse

Prior research suggests that drug abuse (DA) is strongly influenced by both genetic and familial environmental factors. No large-scale adoption study has previously attempted to verify and integrate these findings. To determine how genetic and environmental factors contribute to the risk for DA. Follow-up in 9 public databases (1961-2009) of adopted children and their biological and adoptive relatives. Sweden. The study included 18 115 adopted children born between 1950 and 1993; 78,079 biological parents and siblings; and 51,208 adoptive parents and siblings. Drug abuse recorded in medical, legal, or pharmacy registry records. Risk for DA was significantly elevated in the adopted offspring of biological parents with DA (odds ratio, 2.09; 95% CI, 1.66-2.62), in biological full and half siblings of adopted children with DA (odds ratio, 1.84; 95% CI, 1.28-2.64; and odds ratio, 1.41; 95% CI, 1.19-1.67, respectively), and in adoptive siblings of adopted children with DA (odds ratio, 1.95; 95% CI, 1.43-2.65). A genetic risk index (including biological parental or sibling history of DA, criminal activity, and psychiatric or alcohol problems) and an environmental risk index (including adoptive parental history of divorce, death, criminal activity, and alcohol problems, as well as an adoptive sibling history of DA and psychiatric or alcohol problems) both strongly predicted the risk for DA. Including both indices along with sex and age at adoption in a predictive model revealed a significant positive interaction between the genetic and environmental risk indices. Drug abuse is an etiologically complex syndrome strongly influenced by a diverse set of genetic risk factors reflecting a specific liability to DA, by a vulnerability to other externalizing disorders, and by a range of environmental factors reflecting marital instability, as well as psychopathology and criminal behavior in the adoptive home. Adverse environmental effects on DA are more pathogenic in individuals with high levels of genetic risk. These results should be interpreted in the context of limitations of the diagnosis of DA from registries.

Multiplex sibling history of coronary heart disease is a strong risk factor for coronary heart disease

Familial risks for coronary heart disease (CHD) in families with multiple affected siblings have not been thoroughly studied. This nationwide cohort study aimed to determine familial risks for hospitalization or death due to CHD in families with multiple affected siblings. The study is a nationwide follow-up study. The Swedish Multigeneration Register data on 0-76-year-old subjects were linked to Hospital Discharge Register and Cause of Death Register data for 1964-2008. Standardized incidence ratios (SIRs) were calculated for individuals whose siblings were hospitalized or died (without previous hospitalization, i.e., primary fatal cases) due to CHD compared with those whose siblings were not affected. The procedure was repeated for spouses. Among a total of 185 810 cases of hospitalization or death due to CHD, the SIRs for hospitalization and death in the siblings of affected probands were 1.82 (95% CI: 1.27-2.60) and 1.60 (95% CI: 1.10-2.36), respectively. The SIRs for hospitalization in siblings of two and three affected probands were 6.92 (95% CI: 4.77-10.03) and 7.88 (95% CI: 5.31-11.70), respectively. The SIRs for death in siblings of two and three affected probands were 7.31 (95% CI: 4.76-11.19) and 6.61 (95% CI: 3.91-11.10), respectively. Spouses had low overall familial risks (SIR = 1.05, 95% CI: 1.05-1.06). Family history of multiple affected siblings increases the CHD risk. Family history is not a binary trait. There are degrees of risk associated with family history with more than one affected sibling.

Epidemiological measures of childhood asthma: Cross-sectional and longitudinal consistency

Defining childhood asthma varies considerably, and the extent of agreement between various measures is not clearly understood in the absence of a recognized 'gold standard'. We compared different definitions of childhood asthma, identified characteristics that might have influenced their accuracy and an acquisition of an 'asthma' label in wheezy and treated children. Using a prospective, population-based birth cohort of 623 children followed up to the age of 14 years the concordance between parental opinion, doctor's diagnosis reported by the parent and asthma's diagnosis in general practice (GP) was analysed using latent class analysis (LCA). At the age of eight, 'ever asthma' prevalences ranged from 15.5% (parental opinion) to 21.5% (GP record). 35% of children by the age of eight years had at least one reported label of asthma, reflecting both cross sectional and longitudinal inconsistencies. By the age of 14 years, 16% of children were inconsistently defined as 'ever asthmatic' by their parents. The prevalence of 'ever asthma' estimated by LCA was 19.3%, indicating a parental report of a doctor's diagnosis to be the most sensitive and specific definition. The likelihood of being labelled with asthma was higher in those with a parental or sibling history of asthma, but not determined by socio-demographic characteristics. Although the estimates of prevalence were similar for parental reports and GP records, agreement between the three sources was less than expected. Parental report of a doctor's diagnosis of asthma is sensitive, specific, longitudinally consistent and not subject to large socio-economic bias.